SHH 对 MCAO 模型大鼠血管新生的影响及作用机制

摘要

Objective To explore the effect of the activated sonic hedgehog signaling ( SHH) signaling pathway on neovascularization of model rats with middle cerebral artery occlusion ( MCAO) .Methods Thirty-six MCAO model rats were induced by suture-occluded method and then were randomly divided into three groups , 12 in each group:the sham op-eration group, control group and observation group .Rats in the observation group received lateral ventricle injection of 2μL SHH protein (1 μg/μL), and the same amount of PBS was injected into rats of the control and sham operation groups . Three days or 7 days after intervention , we examined the neurological deficits , cerebral blood flow ( CBF) and infarct vol-ume.The expression levels of vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang-1) in the ischemic cor-tex around the infarction area were detected by RT-PCR and Western blotting .Results The neurological score:after in-tervention for 3 and 7 days, the observation group was lower than the control group , and the control group was higher than the sham operation group (all P<0.05).CBF:after intervention for 3 and 7 days, the increase of the observation group was more significant than that of the control group , and the decrease of the control group decreased more significantly than that of the sham operation group (all P<0.05).Cerebral infarction volume:after intervention for 3 and 7 days, the obser-vation group was obviously less than the control group , and the control group were significantly greater than the sham opera-tion group (all P<0.05).VEGF and Ang-1 expression:after intervention for 3 and 7 d, the observation group was signifi-cantly higher than the control group , and the control group were significantly lower than the sham operation group ( all P<0.05).Conclusion Activation of SHH protein can promote neovascularization of MCAO model rats , whose mechanism may be related with the up-regulation of VEGF and Ang-1.%目的：探讨特异性激活SHH信号通路对大脑中动脉脑梗死大鼠血管新生的影响。方法采用线栓法将36只大鼠制作大脑中动脉梗死（ MCAO）模型并随机分为观察组、对照1组、对照2组各12只，观察组于左侧侧脑室注射1μg／μL的SHH（ sonic hedgehog ）蛋白注射液2μL，对照1组及对照2组注射等量PBS。观察各组干预3、7 d神经功能评分、脑血流值、脑梗死体积，采用半定量PCR及免疫印迹技术检测梗塞核心区周围的缺血皮层内血管内皮生长因子（VEGF）、血管生成素-1（Ang-1）表达水平。结果神经功能评分：干预3、7 d观察组均低于对照1组，对照1组均高于对照2组，P均＜0．05。脑血流值：干预3、7 d观察组上升均较对照1组明显，对照1组下降较对照2组明显；P均＜0．05。脑梗死体积：干预3、7 d观察组脑均明显小于对照1组，对照1组均明显大于对照2组，P均＜0．05。 VEGF、Ang-1表达：干预3、7 d观察组均明显高于对照1组，对照1组均明显低于对照2组，P均＜0．05。结论 SHH蛋白可促进MCAO模型大鼠的血管新生，其机制可能为上调VEGF、Ang-1的表达水平。